A 2016 study by researcher David Arterburn and colleagues in the Journal of Clinical Medicine suggests that taking an antidepressant for two years is associated with an increase in body weight. Luckily, bupropion (trade name Wellbutrin) is an exception that may be a good choice for obese or overweight patients.

The researchers analyzed links between which antidepressants patients in a large health system in Washington State were prescribed and their body weight two years later.

The researchers used fluoxetine (Prozac) as a reference. Most antidepressants did not differ significantly from fluoxetine in terms of the weight gain experienced by people taking the drug.

There were a few exceptions. Compared to non-smoking fluoxetine users, who gained an average of 4.6 pounds in two years, non-smoking bupropion users actually lost weight—an average of 2.4 pounds. (Smokers taking bupropion still gained an average of 6.9 pounds.)

Sertraline (Zoloft) was another exception. Sertraline users gained more than users of other antidepressants—an average of 10.5 pounds over two years.

A 2012 study by Geoge I. Papkostas and colleagues found that 15mg/day of the nutritional supplement l-methylfolate calcium (a form of the B vitamin folate that the body can more readily use) improved depression in people who had not responded adequately to treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant. In a follow-up study by Richard C. Shelton and colleagues published in the Journal of Clinical Psychiatry in 2015, the same researchers further analyzed these data and found that l-methylfolate worked better in patients who were overweight (with body mass indexes (BMIs) of 30 or above) and those who had higher than average levels of inflammation at the beginning of the study. Inflammatory markers linked to greater improvement with l-methylfolate included TNF-alpha, IL-8, high sensitivity CRP, and leptin. In overweight participants, higher than average levels of IL-6 were also linked to more improvement on l-methylfolate.

In an abstract presented at the 5th Biennial Conference of the International Society for Bipolar Disorders, K. Sim and colleagues discussed the impact of increased body mass index on the integrity of white matter in the brain during a first episode of mania. The researchers found significant abnormalities in white matter integrity in the temporal pole and occipital brain regions in overweight and obese patients compared to patients of normal weight. These data highlight the need to clarify the neural mechanisms that link obesity and poorer functional outcomes in bipolar disorder.

Other investigators have reported that bipolar patients with obesity have a less robust response to naturalistic treatment compared to those of normal weight. At least one study suggested that patients with overweight and obesity experience more cognitive difficulties.

Editor’s Note: The pathophysiological mechanisms involved in the relationship between weight and brain function are not yet clear, although one possibility is that in obese patients, some fat cells in the abdominal area become too big to survive and are scavenged by other cytokine-producing cells. These inflammatory cytokines are then able to cross the blood-brain barrier, enter the brain, and affect neuronal functioning. Whether a mechanism like this is at play in relation to these particular findings remains for further investigation.

Nonetheless, these data suggest the importance of good diet, exercise, and other means of maintaining a good body weight in order to attempt to avoid some of the adverse associations of obesity with deficits in cognition, white matter integrity, and treatment outcome.

Although the editors of BipolarNews.org have made every effort to report accurate information, much of the work referenced here is in abstract or pre-publication form, and may not have received proper review by the scientific community at this time. Patients should consult with their physicians about any treatment decisions. Physicians should consult the peer-reviewed literature.